Links between environment tobacco smoke (ETS) and cardiovascular diseases in adults are well established. Many forms of chronic cardiovascular disease are initiated in childhood and/or young adulthood, and at least one quarter of children in the United States are exposed to ETS. In addition to ETS, childhood overweight and obesity (affecting about one-third of the pediatric population) is an important independent risk factor associated with cardiovascular disease in adulthood. Several recent studies in adult humans and animals suggest that obesity is a setting of chronic systemic inflammation, leading to metabolic and cardiovascular consequences. Although ETS, adiposity and inflammation often co-exist in children, their relationships and their impact on vascular performance prior to adult disease have not been addressed. Our hypothesis is that inflammation, endothelial dysfunction and oxidative stress caused by ETS are potentiated by obesity and effect vascular function in children. The overall goal is to improve the health of children and adults through research on the early development of cardiovascular disease, especially in the presence of ETS. Our aims are to: 1. Test the hypothesis that ETS induced vascular dysfunction in children is magnified in the presence of obesity. ETS-exposed and unexposed children ages 9-18 will be recruited. Children with normal BMI (<85% per age) and elevated BMI (>95% per age) will be studied in parallel. Forearm blood flow (FBF) will be determined by plethysmography as an assessment of endothelial performance in vivo. Vascular performance will be investigated in relation to vascular responses, blood lipids, inflammation markers, adiponectin, oxidative stress, and endothelial injury. 2. Test the hypothesis that circulating levels of endothelial progenitor cells (EPC) are predicted by ETS exposures in children and that obesity magnifies this effect. EPC counts will be determined in normal weight and obese youth and adolescents (both exposed and unexposed to ETS) by flow cytometry. EPC concentrations will be related to vascular responses, blood lipids, inflammation markers, adiponectin, oxidative stress, and endothelial injury. Relationships between degree and duration of ETS exposure and measured endpoints will be determined with covariate regression analyses and preliminary structural equation modeling. Defining the relationship and mechanisms of multi-risk factors (ETS and obesity) for cardiovascular disease in childhood as a result of this study will have significant implications for child and adult health. PUBLIC HEALTH RELEVANCE: The scientific links between environment tobacco smoke (ETS) and heart diseases, the number one killer in the country, in adults are well established. The relationship between ETS exposure and damage to the heart and blood vessels during childhood has not been studied. Meanwhile, childhood obesity has recently been described as the "new pandemic of the new millennium" and also has negative effects on heart health. The objective of this study is to define the relationship between ETS, obesity, and blood vessel function in children. A result of this study will have significant implications for child and adult health.